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623 results on '"Ashley, David M."'

201. Machine-learning prediction of cancer survival: a retrospective study using electronic administrative records and a cancer registry

Author

Gupta, Sunil, primary, Tran, Truyen, additional, Luo, Wei, additional, Phung, Dinh, additional, Kennedy, Richard Lee, additional, Broad, Adam, additional, Campbell, David, additional, Kipp, David, additional, Singh, Madhu, additional, Khasraw, Mustafa, additional, Matheson, Leigh, additional, Ashley, David M, additional, and Venkatesh, Svetha, additional

Published
2014
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202. The oncogenic properties of EWS/WT1 of desmoplastic small round cell tumors are unmasked by loss of p53 in murine embryonic fibroblasts

Author

Bandopadhayay, Pratiti, Jabbour, Anissa M, Riffkin, Christopher, Salmanidis, Marika, Gordon, Lavinia, Popovski, Dean, Rigby, Lin, Ashley, David M., Watkins, David N., Thomas, David M., Algar, Elizabeth, Ekert, Paul G., Bandopadhayay, Pratiti, Jabbour, Anissa M, Riffkin, Christopher, Salmanidis, Marika, Gordon, Lavinia, Popovski, Dean, Rigby, Lin, Ashley, David M., Watkins, David N., Thomas, David M., Algar, Elizabeth, and Ekert, Paul G.

Abstract

BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is characterized by the presence of a fusion protein EWS/WT1, arising from the t (11;22) (p13;q12) translocation. Here we examine the oncogenic properties of two splice variants of EWS/WT1, EWS/WT1-KTS and EWS/WT1 + KTS. METHODS: We over-expressed both EWS/WT1 variants in murine embryonic fibroblasts (MEFs) of wild-type, p53+/- and p53-/- backgrounds and measured effects on cell-proliferation, anchorage-independent growth, clonogenicity after serum withdrawal, and sensitivity to cytotoxic drugs and gamma irradiation in comparison to control cells. We examined gene expression profiles in cells expressing EWS/WT1. Finally we validated our key findings in a small series of DSRCT. RESULTS: Neither isoform of EWS/WT1 was sufficient to transform wild-type MEFs however the oncogenic potential of both was unmasked by p53 loss. Expression of EWS/WT1 in MEFs lacking at least one allele of p53 enhanced cell-proliferation, clonogenic survival and anchorage-independent growth. EWS/WT1 expression in wild-type MEFs conferred resistance to cell-cycle arrest after irradiation and daunorubicin induced apoptosis. We show DSRCT commonly have nuclear localization of p53, and copy-number amplification of MDM2/MDMX. Expression of either isoform of EWS/WT1 induced characteristic mRNA expression profiles. Gene-set enrichment analysis demonstrated enrichment of WNT pathway signatures in MEFs expressing EWS/WT1 + KTS. Wnt-activation was validated in cell lines with over-expression of EWS/WT1 and in DSRCT. CONCLUSION: In conclusion, we show both isoforms of EWS/WT1 have oncogenic potential in MEFs with loss of p53. In addition we provide the first link between EWS/WT1 and Wnt-pathway signaling. These data provide novel insights into the function of the EWS/WT1 fusion protein which characterize DSRCT.

Published
2013

204. Sustained low-dose treatment with the histone deacetylase inhibitor LBH589 induces terminal differentation of osteosarcoma cells

Author

Cain, Jason E., McCaw, Andrew, Jayasekara, W. Samantha N., Rossello, Fernando J., Marini, Kieren D., Irving, Aaron T., Kansara, Maya, Thomas, David M., Ashley, David M., Watkins, D. Neil, Cain, Jason E., McCaw, Andrew, Jayasekara, W. Samantha N., Rossello, Fernando J., Marini, Kieren D., Irving, Aaron T., Kansara, Maya, Thomas, David M., Ashley, David M., and Watkins, D. Neil

Published
2013

205. Enhanced lithium-induced brain recovery following cranial irradiation is not impeded by inflammation

Author

Malaterre, Jordane, McPherson, Cameron S., Denoyer, Delphine, Lai, Emily, Hagekyriakou, Jim, Lightowler, Sally, Shudo, Koishi, Ernst, Matthias, Ashley, David M., Short, Jennifer L., Wheeler, Greg, Ramsay, Robert G, Malaterre, Jordane, McPherson, Cameron S., Denoyer, Delphine, Lai, Emily, Hagekyriakou, Jim, Lightowler, Sally, Shudo, Koishi, Ernst, Matthias, Ashley, David M., Short, Jennifer L., Wheeler, Greg, and Ramsay, Robert G

Published
2012

206. High expression of BMP pathway genes distinguishes a subset of atypical teratoid/rhabdoid tumors associated with shorter survival

Author

Birks, Diane K., Donson, Andrew M., Patel, Purvi R., Dunham, Christopher, Muscat, Andrea, Algar, Elizabeth M., Ashley, David M., Kleinschmidt-Demasters, B. K., Vibhakar, Rajeev, Handler, Michael H., Foreman, Nicholas K., Birks, Diane K., Donson, Andrew M., Patel, Purvi R., Dunham, Christopher, Muscat, Andrea, Algar, Elizabeth M., Ashley, David M., Kleinschmidt-Demasters, B. K., Vibhakar, Rajeev, Handler, Michael H., and Foreman, Nicholas K.

Abstract

Molecular profiling of tumors has proven to be a valuable tool for identification of prognostic and diagnostic subgroups in medulloblastomas, glioblastomas, and other cancers. However, the molecular landscape of atypical teratoid/rhabdoid tumors (AT/RTs) remains largely unexplored. To address this issue, we used microarrays to measure the gene expression profiles of 18 AT/RTs and performed unsupervised hierarchical clustering to determine molecularly similar subgroups. Four major subgroups (clusters) were identified. These did not conform to sex, tumor location, or presence of monosomy 22. Clusters showed distinct gene signatures and differences in enriched biological processes, including elevated expression of some genes associated with choroid plexus lineage in cluster 4. In addition, survival differed significantly by cluster, with shortest survival (mean, 4.7 months) in both clusters 3 and 4, compared with clusters 1 and 2 (mean, 28.1 months). Analysis showed that multiple bone morphogenetic protein (BMP) pathway genes were upregulated in the short survival clusters, with BMP4 showing the most significant upregulation (270-fold). Thus, high expression of BMP pathway genes was negatively associated with survival in this dataset. Our study indicates that molecular subgroups exist in AT/RTs and that molecular profiling of these comparatively rare tumors may be of diagnostic, prognostic, and therapeutic value.

Published
2011

207. Rapid detection of SMARCB1 sequence variation using high resolution melting

Author

Dagar, Vinod, Chow, Chung-Wo, Ashley, David M., Algar, Elizabeth M., Dagar, Vinod, Chow, Chung-Wo, Ashley, David M., and Algar, Elizabeth M.

Abstract

Background : Rhabdoid tumors are rare cancers of early childhood arising in the kidney, central nervous system and other organs. The majority are caused by somatic inactivating mutations or deletions affecting the tumor suppressor locus SMARCB1 [OMIM 601607]. Germ-line SMARCB1 inactivation has been reported in association with rhabdoid tumor, epitheloid sarcoma and familial schwannomatosis, underscoring the importance of accurate mutation screening to ascertain recurrence and transmission risks. We describe a rapid and sensitive diagnostic screening method, using high resolution melting (HRM), for detecting sequence variations in SMARCB1. Methods : Amplicons, encompassing the nine coding exons of SMARCB1, flanking splice site sequences and the 5' and 3' UTR, were screened by both HRM and direct DNA sequencing to establish the reliability of HRM as a primary mutation screening tool. Reaction conditions were optimized with commercially available HRM mixes. Results : The false negative rate for detecting sequence variants by HRM in our sample series was zero. Nine amplicons out of a total of 140 (6.4%) showed variant melt profiles that were subsequently shown to be false positive. Overall nine distinct pathogenic SMARCB1 mutations were identified in a total of 19 possible rhabdoid tumors. Two tumors had two distinct mutations and two harbored SMARCB1 deletion. Other mutations were nonsense or frame-shifts. The detection sensitivity of the HRM screening method was influenced by both sequence context and specific nucleotide change and varied from 1: 4 to 1:1000 (variant to wild-type DNA). A novel method involving digital HRM, followed by re-sequencing, was used to confirm mutations in tumor specimens containing associated normal tissue. Conclusions : This is the first report describing SMARCB1 mutation screening using HRM. HRM is a rapid, sensitive and inexpensive screening technology that is likely to be widely adopted in diagnostic laboratories to facilitate whole gene

Published
2009

208. Imprinted CDKN1C is a tumor suppressor in rhabdoid tumor and activated by restoration of SMARCB1 and histone deacetylase inhibitors

Author

Algar, Elizabeth M., Muscat, Andrea, Dagar, Vinod, Rickert, Christian, Chow, C.W., Biegel, Jaclyn A., Ekert, Paul G., Saffery, Richard, Craig, Jeff, Johnstone, Ricky W., Ashley, David M., Algar, Elizabeth M., Muscat, Andrea, Dagar, Vinod, Rickert, Christian, Chow, C.W., Biegel, Jaclyn A., Ekert, Paul G., Saffery, Richard, Craig, Jeff, Johnstone, Ricky W., and Ashley, David M.

Abstract

SMARCB1 is deleted in rhabdoid tumor, an aggressive paediatric malignancy affecting the kidney and CNS. We hypothesized that the oncogenic pathway in rhabdoid tumors involved epigenetic silencing of key cell cycle regulators as a consequence of altered chromatin-remodelling, attributable to loss of SMARCB1, and that this hypothesis if proven could provide a biological rationale for testing epigenetic therapies in this disease. We used an inducible expression system to show that the imprinted cell cycle inhibitor CDKN1C is a downstream target for SMARCB1 and is transcriptionally activated by increased histone H3 and H4 acetylation at the promoter. We also show that CDKN1C expression induces cell cycle arrest, CDKN1C knockdown with siRNA is associated with increased proliferation, and is able to compete against the anti-proliferative effect of restored SMARCB1 expression. The histone deacetylase inhibitor (HDACi), Romidepsin, specifically restored CDKN1C expression in rhabdoid tumor cells through promoter histone H3 and H4 acetylation, recapitulating the effect of SMARCB1 on CDKNIC allelic expression, and induced cell cycle arrest in G401 and STM91-01 rhabdoid tumor cell lines. CDKN1C expression was also shown to be generally absent in clinical specimens of rhabdoid tumor, however CDKN1A and CDKN1B expression persisted. Our observations suggest that maintenance of CDKN1C expression plays a critical role in preventing rhabdoid tumor growth. Significantly, we report for the first time, parallels between the molecular pathways of SMARCB1 restoration and Romidepsin treatment, and demonstrate a biological basis for the further exploration of histone deacetylase inhibitors as relevant therapeutic reagents in the treatment of rhabdoid tumor.

Published
2009

209. Efficacy and cost-effectiveness of an outcall program to reduce carer burden and depression among carers of cancer patients [PROTECT]: rationale and design of a randomized controlled trial

Author

Livingston, Patricia M, primary, Osborne, Richard H, additional, Botti, Mari, additional, Mihalopoulos, Cathy, additional, McGuigan, Sean, additional, Heckel, Leila, additional, Gunn, Kate, additional, Chirgwin, Jacquie, additional, Ashley, David M, additional, and Williams, Melinda, additional

Published
2014
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210. Epigenetic deregulation in pediatric acute lymphoblastic leukemia

Author

Chatterton, Zac, primary, Morenos, Leah, additional, Mechinaud, Francoise, additional, Ashley, David M, additional, Craig, Jeffrey M, additional, Sexton-Oates, Alexandra, additional, Halemba, Minhee S, additional, Parkinson-Bates, Mandy, additional, Ng, Jane, additional, Morrison, Debra, additional, Carroll, William L, additional, Saffery, Richard, additional, and Wong, Nicholas C, additional

Published
2014
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211. The oncogenic properties of EWS/WT1 of desmoplastic small round cell tumors are unmasked by loss of p53 in murine embryonic fibroblasts

Author

Bandopadhayay, Pratiti, primary, Jabbour, Anissa M, additional, Riffkin, Christopher, additional, Salmanidis, Marika, additional, Gordon, Lavinia, additional, Popovski, Dean, additional, Rigby, Lin, additional, Ashley, David M, additional, Watkins, David N, additional, Thomas, David M, additional, Algar, Elizabeth, additional, and Ekert, Paul G, additional

Published
2013
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212. Medulloblastoma Down Under 2013: a report from the third annual meeting of the International Medulloblastoma Working Group

Author

Gottardo, Nicholas G., primary, Hansford, Jordan R., additional, McGlade, Jacqueline P., additional, Alvaro, Frank, additional, Ashley, David M., additional, Bailey, Simon, additional, Baker, David L., additional, Bourdeaut, Franck, additional, Cho, Yoon-Jae, additional, Clay, Moira, additional, Clifford, Steven C., additional, Cohn, Richard J., additional, Cole, Catherine H., additional, Dallas, Peter B., additional, Downie, Peter, additional, Doz, François, additional, Ellison, David W., additional, Endersby, Raelene, additional, Fisher, Paul G., additional, Hassall, Timothy, additional, Heath, John A., additional, Hii, Hilary L., additional, Jones, David T. W., additional, Junckerstorff, Reimar, additional, Kellie, Stewart, additional, Kool, Marcel, additional, Kotecha, Rishi S., additional, Lichter, Peter, additional, Laughton, Stephen J., additional, Lee, Sharon, additional, McCowage, Geoff, additional, Northcott, Paul A., additional, Olson, James M., additional, Packer, Roger J., additional, Pfister, Stefan M., additional, Pietsch, Torsten, additional, Pizer, Barry, additional, Pomeroy, Scott L., additional, Remke, Marc, additional, Robinson, Giles W., additional, Rutkowski, Stefan, additional, Schoep, Tobias, additional, Shelat, Anang A., additional, Stewart, Clinton F., additional, Sullivan, Michael, additional, Taylor, Michael D., additional, Wainwright, Brandon, additional, Walwyn, Thomas, additional, Weiss, William A., additional, Williamson, Dan, additional, and Gajjar, Amar, additional

Published
2013
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214. Pulmonary function after treatment for embryonal brain tumors on SJMB03 that included craniospinal irradiation.

Author

Green, Daniel M., primary, Merchant, Thomas E., additional, Billups, Catherine A, additional, Stokes, Dennis C, additional, Broniscer, Alberto, additional, Srinivasan, Ashok, additional, Chintagumpala, Murali M., additional, Hassall, Timothy E, additional, Bouffet, Eric, additional, Gururangan, Sridharan, additional, Kellie, Stewart J, additional, Ashley, David M, additional, Cohn, Richard J, additional, Fisher, Michael J., additional, and Gajjar, Amar J., additional

Published
2013
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220. Induction Chemotherapy and Conformal Radiation Therapy for Very Young Children With Nonmetastatic Medulloblastoma: Children's Oncology Group Study P9934

Author

Ashley, David M., primary, Merchant, Thomas E., additional, Strother, Douglas, additional, Zhou, Tianni, additional, Duffner, Patricia, additional, Burger, Peter C., additional, Miller, Douglas C., additional, Lyon, Nancy, additional, Bonner, Melanie J., additional, Msall, Michael, additional, Buxton, Allen, additional, Geyer, Russell, additional, Kun, Larry E., additional, Coleman, Lee, additional, and Pollack, Ian F., additional

Published
2012
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221. Enhanced Lithium-Induced Brain Recovery Following Cranial Irradiation Is Not Impeded by Inflammation

Author

Malaterre, Jordane, primary, McPherson, Cameron S., additional, Denoyer, Delphine, additional, Lai, Emily, additional, Hagekyriakou, Jim, additional, Lightowler, Sally, additional, Shudo, Koishi, additional, Ernst, Matthias, additional, Ashley, David M., additional, Short, Jennifer L., additional, Wheeler, Greg, additional, and Ramsay, Robert G., additional

Published
2012
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222. A phase I/II study of LDE225, a smoothened (Smo) antagonist, in pediatric patients with recurrent medulloblastoma (MB) or other solid tumors.

Author

Geoerger, Birgit, primary, Aerts, Isabelle, additional, Casanova, Michela, additional, Chisholm, Julia C., additional, Hargrave, Darren R, additional, Leary, Sarah, additional, Ashley, David M, additional, Bouffet, Eric, additional, MacDonald, Tobey, additional, Hurh, Eunju, additional, Dey, Jyotirmoy, additional, Kalambakas, Stacey, additional, Amakye, Dereck Dokyi, additional, and Kieran, Mark W., additional

Published
2012
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225. Results of a phase 1 study utilizing monocyte-derived dendritic cells pulsed with tumor RNA in children and young adults with brain cancer

Author

Caruso, Denise A, Orme, Lisa M, Neale, Alana M, Radcliff, Fiona J, Amor, Gerlinda M, Maixner, Wirginia, Downie, Peter, Hassall, Timothy E, Tang, Mimi LK, Ashley, David M, Caruso, Denise A, Orme, Lisa M, Neale, Alana M, Radcliff, Fiona J, Amor, Gerlinda M, Maixner, Wirginia, Downie, Peter, Hassall, Timothy E, Tang, Mimi LK, and Ashley, David M

Published
2004

226. High expression of BMP pathway genes distinguishes a subset of atypical teratoid/rhabdoid tumors associated with shorter survival

Author

Birks, Diane K., primary, Donson, Andrew M., additional, Patel, Purvi R., additional, Dunham, Christopher, additional, Muscat, Andrea, additional, Algar, Elizabeth M., additional, Ashley, David M., additional, Kleinschmidt-DeMasters, B. K., additional, Vibhakar, Rajeev, additional, Handler, Michael H., additional, and Foreman, Nicholas K., additional

Published
2011
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229. Imprinted CDKN1C Is a Tumor Suppressor in Rhabdoid Tumor and Activated by Restoration of SMARCB1 and Histone Deacetylase Inhibitors

Author

Algar, Elizabeth M., primary, Muscat, Andrea, additional, Dagar, Vinod, additional, Rickert, Christian, additional, Chow, C. W., additional, Biegel, Jaclyn A., additional, Ekert, Paul G., additional, Saffery, Richard, additional, Craig, Jeff, additional, Johnstone, Ricky W., additional, and Ashley, David M., additional

Published
2009
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234. Multi-Institution Prospective Trial of Reduced-Dose Craniospinal Irradiation (23.4 Gy) Followed by Conformal Posterior Fossa (36 Gy) and Primary Site Irradiation (55.8 Gy) and Dose-Intensive Chemotherapy for Average-Risk Medulloblastoma

Author

Merchant, Thomas E., primary, Kun, Larry E., additional, Krasin, Matthew J., additional, Wallace, Dana, additional, Chintagumpala, Murali M., additional, Woo, Shiao Y., additional, Ashley, David M., additional, Sexton, Maree, additional, Kellie, Stewart J., additional, Ahern, Verity, additional, and Gajjar, Amar, additional

Published
2008
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236. Unarmed, tumor-specific monoclonal antibody effectively treats brain tumors

Author

Sampson, John H, Crotty, Laura E, Lee, Samson, Archer, Gary E, Ashley, David M, Wikstrand, Carol J, Hale, Laura P, Small, Clayton, Dranoff, Glenn, Friedman, Allan H, Friedman, Henry S, Bigner, Darell D, Sampson, John H, Crotty, Laura E, Lee, Samson, Archer, Gary E, Ashley, David M, Wikstrand, Carol J, Hale, Laura P, Small, Clayton, Dranoff, Glenn, Friedman, Allan H, Friedman, Henry S, and Bigner, Darell D

Published
2000

241. Risk Assessment of Space Debris Hazards for Global Positioning Spacecraft

Author

AIR FORCE INST OF TECH WRIGHT-PATTERSONAFB OH, Ashley, David M., AIR FORCE INST OF TECH WRIGHT-PATTERSONAFB OH, and Ashley, David M.

Abstract

An important concern of USSPACECOM has been developing a policy to reduce orbital debris, including ensuring proper spacecraft end-of-life disposal to minimize the number of spacecraft left on mission orbit beyond their useful lifetimes. This paper provides insight to the pertinent issues related to space debris and spacecraft disposal in addition to a detailed analysis of debris hazards for the Global Positioning System (GPS) family of spacecraft as outlined by M. E. Sorge. Results of the analysis show that inactive GPS satellites pose the most significant hazard to the GPS constellation of all space debris of large size, thus reaffirming recent U.S. space policy mandating deorbiting for all GPS satellites deemed non-mission capable. Additional analysis is recommended to explore collision probabilities for medium sized debris, since this category is also capable of disabling GPS satellites.

Published
1998

248. Unarmed, tumor-specific monoclonal antibody effectively treats brain tumors

Author

Sampson, John H., primary, Crotty, Laura E., additional, Lee, Samson, additional, Archer, Gary E., additional, Ashley, David M., additional, Wikstrand, Carol J., additional, Hale, Laura P., additional, Small, Clayton, additional, Dranoff, Glenn, additional, Friedman, Allan H., additional, Friedman, Henry S., additional, and Bigner, Darell D., additional

Published
2000
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249. A protocol for a discrete choice experiment: understanding preferences of patients with cancer towards their cancer care across metropolitan and rural regions in Australia.

Author

Shu Fen Wong, Norman, Richard, Dunning, Trisha L., Ashley, David M., and Lorgelly, Paula K.

Abstract

Introduction: Medical decision-making in oncology is a complicated process and to date there are few studies examining how patients with cancer make choices with respect to different features of their care. It is also unknown whether patient choices vary by geographical location and how location could account for observed rural and metropolitan cancer differences. This paper describes an ongoing study that aims to (1) examine patient and healthcare-related factors that influence choices of patients with cancer; (2) measure and quantify preferences of patients with cancer towards cancer care using a discrete choice experiment (DCE) and (3) explore preference heterogeneity between metropolitan and rural locations. Methods and analysis: A DCE is being conducted to understand how patients with cancer choose between two clinical scenarios accounting for different patient and healthcare-related factors (and levels). Preliminary qualitative research was undertaken to guide the development of an appropriate DCE design including characteristics that are important and relevant to patients with cancer. A fractional factorial design using the D-efficiency criteria was used to estimate interactions among attributes. Multinomial logistic regression will be used for the primary DCE analysis and to control for sociodemographic and clinical characteristics. Ethics and dissemination: The Barwon Health Human Research Ethics Committee approved the study. Findings from the study will be presented in national/ international conferences and peer-reviewed journals. Our results will form the basis of a feasibility study to inform the development of a larger scale study into preferences of patients with cancer and their association with cancer outcomes. [ABSTRACT FROM AUTHOR]

Published
2014
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250. Characteristics of cancer diagnoses and staging in South Western Victoria: A rural perspective.

Author

Banks, Patricia, Matheson, Leigh M., Morrissy, Kate, Olesen, Inger, Pitson, Graham, Chapman, Adam, Ashley, David M., and Henry, Margaret J.

Subjects
TUMOR diagnosis, BREAST tumors, CHI-squared test, PROSTATE tumors, RURAL conditions, TUMORS, TUMOR classification, DISEASE incidence, RETROSPECTIVE studies
Abstract

Objective Australian states and territories have legislation mandating reporting of cancer diagnoses; however, tumour stage at diagnosis, treatment plan and associated outcomes are not routinely recorded in cancer registries for all tumour types. This study describes the Evaluation of Cancer Outcomes study that collects detailed information for patients diagnosed with cancer in south-western Victoria. Design Retrospective data collection. Setting Population based. Participants New cancer patients within the Barwon South Western region. Main outcome measures Cancer incidence and staging data for a regional and rural area. Results In 2009, there were 1778 primary tumours. Prominent tumour streams included prostate, breast, colon, lung, lymphoma, melanoma and rectum. Stage at diagnosis was recorded for more than 50% of patients for the tumour streams of testis, breast, bowel, renal, lung, and head and neck. Patients reporting to health centres with an on-site oncologist as part of their team had a higher rate of staging recorded at diagnosis (48.0 versus 36.9%, P = 0.01). More women (55.4%) than men (41.4%) had stage-recorded. Conclusion The Evaluation of Cancer Outcomes study is an important initiative that collects information about newly diagnosed cases of cancer more detailed than is currently collected by the Cancer Council of Victoria. Future studies will build on this base dataset and provide valuable insight into the regional and rural experience of treatment pathways after diagnosis. More work is needed to bring more services to our rural patients, or more education is needed to encourage the recording of tumour staging. [ABSTRACT FROM AUTHOR]

Published
2014
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